Rapidly dissolving fibroin microneedles for transdermal drug delivery

Abstract This paper presents rapidly dissolving fibroin microneedles (MNs) for the first time. A reverse PDMS MNs mold was first created and drug-contained fibroin solution was poured into this reverse PDMS MNs mold. Fibroin MNs were successfully fabricated after fan drying and detaching the solidified drug-contained fibroin structure from the PDMS mold. The fibroin serves as a matrix to incorporate drug molecules while maintaining the drug activity. The dimensions of the fabricated fibroin MNs are 500 μm in length, 200 μm in diameter at the base, and 5 μm in radius at the tip. These fibroin MNs can dissolve within minutes under the skin to release the drug molecules and the dissolved fibroin in the skin generates noninflammatory amino acid degradation products usable in cell metabolic functions. The fibroin MNs containing methylene blue as a drug were fabricated and their surface morphology, internal structure, mechanical property, and the dissolving characteristics were analyzed. These rapidly dissolving fibroin MNs provide more benefit than conventional syringes for painless transdermal drug delivery.

[1]  David L. Kaplan,et al.  Mechanism of silk processing in insects and spiders , 2003, Nature.

[2]  L. Meinel,et al.  Silk fibroin as a vehicle for drug delivery applications. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[3]  Takaya Miyano,et al.  Sugar Micro Needles as Transdermic Drug Delivery System , 2005, Biomedical microdevices.

[4]  Mark R Prausnitz,et al.  Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. , 2004, Journal of biomechanics.

[5]  Hiromi Yamada,et al.  Preparation of undegraded native molecular fibroin solution from silkworm cocoons , 2001 .

[6]  R. Valluzzi,et al.  Silk I structure in Bombyx mori silk foams. , 1999, International journal of biological macromolecules.

[7]  Mark G. Allen,et al.  Polymer Microneedles for Controlled-Release Drug Delivery , 2006, Pharmaceutical Research.

[8]  D. Kaplan,et al.  In vivo degradation of three-dimensional silk fibroin scaffolds. , 2008, Biomaterials.

[9]  T. Asakura,et al.  Small-diameter vascular grafts of Bombyx mori silk fibroin prepared by a combination of electrospinning and sponge coating , 2010 .

[10]  Shigeo Nakamura,et al.  Physical properties and structure of silk. VI. Conformational changes in silk fibroin induced by immersion in water at 2 to 130°c , 1979 .

[11]  D. Kaplan,et al.  Bioactive "self-sensing" optical systems. , 2009, Applied physics letters.

[12]  K. Mita,et al.  Highly repetitive structure and its organization of the silk fibroin gene , 1994, Journal of Molecular Evolution.

[13]  M. Jacquet,et al.  Fine organization of Bombyx mori fibroin heavy chain gene. , 2000, Nucleic acids research.

[14]  E. Blout,et al.  The Infrared Spectra of Polypeptides in Various Conformations: Amide I and II Bands1 , 1961 .

[15]  Mark R. Prausnitz,et al.  Dissolving Polymer Microneedle Patches for Influenza Vaccination , 2010, Nature Medicine.

[16]  A. Banga,et al.  Molecular charge mediated transport of a 13 kD protein across microporated skin. , 2009, International journal of pharmaceutics.

[17]  F. Kremer,et al.  Similarities in the structural organization of major and minor ampullate spider silk. , 2009, Macromolecular rapid communications.

[18]  Mark R. Prausnitz,et al.  Effect of Microneedle Design on Pain in Human Volunteers , 2008, The Clinical journal of pain.

[19]  Conor O'Mahony,et al.  Processing difficulties and instability of carbohydrate microneedle arrays , 2009, Drug development and industrial pharmacy.

[20]  H. Mantsch,et al.  Protein secondary structure from FT-IR spectroscopy : correlation with dihedral angles from three-dimensional Ramachandran plots , 1991 .

[21]  John A Rogers,et al.  Silicon electronics on silk as a path to bioresorbable, implantable devices. , 2009, Applied physics letters.

[22]  H. Mantsch,et al.  The use and misuse of FTIR spectroscopy in the determination of protein structure. , 1995, Critical reviews in biochemistry and molecular biology.

[23]  Yu-Qing Zhang.  Natural silk fibroin as a support for enzyme immobilization , 1998 .

[24]  Adam J. Davidson,et al.  Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability , 2008 .